Sodium Phenylbutyrate

12/06/2023

4-SODIUM PHENYL BUTYRIC ACID HAS BOTH EFFICACY AND COUNTER-INDICATIVE EFFECTS IN THE TREATMENT OF COL4A1 DISEASE

Abstract

Mutations in the collagen genes COL4A1 and COL4A2 cause Mendelian eye, kidney and cerebrovascular disease including intracerebral haemorrhage (ICH), and common collagen IV variants are a risk factor for sporadic ICH. COL4A1 and COL4A2 mutations cause endoplasmic reticulum (ER) stress and basement membrane (BM) defects, and recent data suggest an association of ER stress with ICH due to a COL4A2 mutation. However, the potential of ER stress as a therapeutic target for the multi-systemic COL4A1 pathologies remains unclear. We performed a preventative oral treatment of Col4a1 mutant mice with the chemical chaperone phenyl butyric acid (PBA), which reduced adult ICH. Importantly, treatment of adult mice with the established disease also reduced ICH. However, PBA treatment did not alter eye and kidney defects, establishing tissue-specific outcomes of targeting Col4a1-derived ER stress, and therefore this treatment may not be applicable for patients with eye and renal disease. While PBA treatment reduced ER stress and increased collagen IV incorporation into BMs, the persistence of defects in BM structure and reduced ability of the BM to withstand mechanical stress indicate that PBA may be counter-indicative for pathologies caused by matrix defects. These data establish that treatment for COL4A1 disease requires a multipronged treatment approach that restores both ER homeostasis and matrix defects. Alleviating ER stress is a valid therapeutic target for preventing and treating established adult ICH, but collagen IV patients will require stratification based on their clinical presentation and mechanism of their mutations.

https://academic.oup.com/hmg/article/28/4/628/5142417

Abstract. Mutations in the collagen genes COL4A1 and COL4A2 cause Mendelian eye, kidney and cerebrovascular disease including intracerebral haemorrhage (ICH), a

10/02/2023

TOPICAL OCULAR SODIUM 4-PHENYLBUTYRATE RESCUES GLAUCOMA IN A MYOCILIN MOUSE MODEL OF PRIMARY OPEN-ANGLE GLAUCOMA

Abstract
Purpose.: Mutations in the myocilin gene (MYOC) are the most common known genetic cause of primary open-angle glaucoma (POAG). The purpose of this study was to determine whether topical ocular sodium 4-phenylbutyrate (PBA) treatment rescues glaucoma phenotypes in a mouse model of myocilin-associated glaucoma (Tg-MYOCY437H mice).

Methods.: Tg-MYOCY437H mice were treated with PBA eye drops (n = 10) or sterile PBS (n = 8) twice daily for 5 months. Long-term safety and effectiveness of topical PBA (0.2%) on glaucoma phenotypes were examined by measuring intraocular pressure (IOP) and pattern ERG (PERG), performing slit lamp evaluation of the anterior chamber, analyzing histologic sections of the anterior segment, and comparing myocilin levels in the aqueous humor and trabecular meshwork of Tg-MYOCY437H mice.

Results.: Tg-MYOCY437H mice developed elevated IOP at 3 months of age when compared with wild-type (WT) littermates (n = 24; P < 0.0001). Topical PBA did not alter IOP in WT mice. However, it significantly reduced elevated IOP in Tg-MYOCY437H mice to the level of WT mice. Topical PBA-treated Tg-MYOCY437H mice also preserved PERG amplitudes compared with vehicle-treated Tg-MYOCY437H mice. No structural abnormalities were observed in the anterior chamber of PBA-treated WT and Tg-MYOCY437H mice. Analysis of the myocilin in the aqueous humor and TM revealed that PBA significantly improved the secretion of myocilin and reduced myocilin accumulation as well as endoplasmic reticulum (ER) stress in the TM of Tg-MYOCY437H mice. Furthermore, topical PBA reduced IOP elevated by induction of ER stress via tunicamycin injections in WT mice.

Conclusions.: Topical ocular PBA reduces glaucomatous phenotypes in Tg-MYOCY437H mice, most likely by reducing myocilin accumulation and ER stress in the TM. Topical ocular PBA could become a novel treatment for POAG patients with myocilin mutations.

https://iovs.arvojournals.org/article.aspx?articleid=2188798

Gulab S. Zode, Kevin E. Bugge, Kabhilan Mohan, Sinisa D. Grozdanic, Joseph C. Peters, Demelza R. Koehn, Michael G. Anderson, Randy H. Kardon, Edwin M. Stone, Val C. Sheffield; Topical Ocular Sodium 4-Phenylbutyrate Rescues Glaucoma in a Myocilin Mouse Model of Primary Open-Angle Glaucoma. Invest. Op...

09/16/2023

WHERE TO PURCHASE - CONTACT US TO ORDER SODIUM PHENYLBUTYRATE

We are the exclusive worldwide supplier of sodium phenylbutyrate for researchers, labs, and compounding pharmacies.

LAB HOUSES

Scandinavian Formulas, Inc. supplies sodium phenylbutyrate to lab houses for their clinical/research customers. Contact us today to place an order.

Scandinavian Formulas, Inc. is the exclusive worldwide supplier of sodium phenylbutyrate to lab houses. Your lab house can subdivide quantities of sodium phenylbutyrate to supply to researchers in the smaller quantities the require.

COMPOUNDING PHARMACIES & PHARMA

We are the global supplier of sodium phenylbutyrate for compounding pharmacies that formulate sodium phenylbutyrate for researchers’ clinical supplies.

Does your compounding pharmacy need sodium phenylbutyrate to create a compound for clinical studies? Scandinavian Formulas, Inc. is the exclusive worldwide supplier of sodium phenylbutyrate for compounding pharmacies.

PATIENTS

At Scandinavian Formulas, Inc., we are sodium phenylbutyrate suppliers to sponsors of clinical investigations which are the subject of an investigational new drug (NDA).

Are you a patient looking for sodium phenylbutyrate suppliers?

Scandinavian Formulas does not supply sodium phenylbutyrate as a treatment. Physicians may wish to review the published list of clinical studies listed on this website to learn where studies are being/have been conducted. Scandinavian Formulas can assist in finding sponsors of various studies.

https://sodiumphenylbutyrate.com/order-sodium-phenylbutyrate/

08/31/2023

SODIUM PHENYLBUTYRATE CANCER RESEARCH

Sodium phenylbutyrate affects glutamine depletion and cell differentiation in cancer cells, as shown in cancer research studies.

Sodium phenylbutyrate (SPB) as a salt of 4-phenylbutyric acid (4-PBA) has been reported to be an ammonia scavenger, histone deacetylase inhibitor, and endoplasmic reticulum stress inhibitor in various diseases, including neurological diseases, inflammatory disorders, and carcinogenesis. Since the early 1990s, sodium phenylbutyrate has been used in clinical studies worldwide. The results of these studies are extremely promising.

CANCER

Cancer, also called malignancy, is an abnormal growth of cells. There are more than 100 types of cancer, including breast cancer, skin cancer, lung cancer, colon cancer, prostate cancer, and lymphoma. Symptoms vary depending on the type. Cancer treatment may include chemotherapy, radiation, and/or surgery.

https://sodiumphenylbutyrate.com/sodium-phenylbutyrate-cancer/

07/07/2023

SODIUM PHENYLBUTYRATE ALS RESEARCH

Sodium phenylbutyrate ALS research studies are contributing to worldwide knowledge about ALS and have shown promising results including prolonged survival, regulated expression of anti-apoptotic genes, and a reduction in neuron loss.

Amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. Voluntary muscles produce movements like chewing, walking, and talking. The disease is progressive, meaning the symptoms get worse over time. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease.

ALS belongs to a wider group of disorders known as motor neuron diseases, which are caused by gradual deterioration and death of motor neurons. Motor neurons are nerve cells that extend from the brain to the spinal cord and muscles throughout the body. These motor neurons initiate and provide vital communication links between the brain and the voluntary muscles.

Messages from motor neurons in the brain, called upper motor neurons, are transmitted to motor neurons in the spinal cord and to motor nuclei of the brain, called lower motor neurons, and from the spinal cord and motor nuclei of the brain to a particular muscle or muscles.
In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken, start to twitch in spasms called fasciculations, and waste away. Eventually, the brain loses its ability to initiate and control voluntary movements.

Early symptoms of ALS usually include muscle weakness or stiffness. Gradually, all muscles under voluntary control are affected, and individuals lose their strength and the ability to speak, eat, move, and even breathe. Most people with ALS die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10% of people with ALS survive for 10 or more years.

https://sodiumphenylbutyrate.com/sodium-phenylbutyrate-als/

06/30/2023

SODIUM PHENYLBUTYRATE USES AND BACKGROUND

Sodium phenylbutyrate was originally developed for Johns Hopkins in the mid-80s as a treatment for inborn errors of urea synthesis metabolic disorders that result in severe mental and psychomotor retardation. In 1996, sodium phenylbutyrate became a viable treatment for urea cycle disorders and is available commercially worldwide for that indication.

Ongoing cancer research has revealed that sodium phenylbutyrate also targets the underlying molecular defects that cause cancer and switches on tumor suppressor genes. It has become a novel anti-cancer therapy that offers lower toxicity than traditional chemotherapy.

Today research continues into new and groundbreaking sodium phenylbutyrate uses including cancer, cystic fibrosis, sickle cell anemia, ALS, Parkinson’s disease, glaucoma, spinal muscular atrophy, tuberculosis, and more.

CHEMICAL STRUCTURE AND METABOLIC ACTION

In terms of its chemical structure, sodium phenylbutyrate is a sodium salt of an aromatic fatty acid composed of an aromatic ring and butyric acid. The chemical name for sodium phenylbutyrate is 4-phenylbutyric acid sodium salt.

Sodium phenylbutyrate may be taken orally or intravenously. It has a naturally salty and slightly bitter taste which may or may not be apparent in its final tablet or powder form.

Although sodium phenylbutyrate is synthetically manufactured, once in the body it is quickly metabolized into a naturally occurring metabolite of phenylalanine. Because it is easily converted to a natural body substance, it has very low toxicity.

https://sodiumphenylbutyrate.com/sodium-phenylbutyrate-uses/

Sodium phenylbutyrate is used to treat urea cycle disorders in people who lack certain liver enzymes needed to eliminate waste substances from the body.

06/23/2023

SODIUM PHENYLBUTYRATE REDUCES REPETITIVE SELF-GROOMING BEHAVIOR AND RESCUES SOCIAL AND COGNITIVE DEFICITS IN MOUSE MODELS OF AUTISM

Abstract

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children. In this study, we assessed the therapeutic effects of NaPB, which is a chemical chaperone as well as histone deacetylase inhibitor on a BTBR T + Itpr3tf/J (BTBR) mice model of ASD. We found that acute and chronic treatment of NaPB remarkably improved, not only core ASD symptoms, including repetitive behaviors and sociability deficit, but also cognitive impairment in the BTBR mice. NaPB substantially induced histone acetylation in the brain of the BTBR mice. Intriguingly, the therapeutic effects of NaPB on autistic-like behaviors, such as repetitive behaviors, impaired sociability, and cognitive deficit also showed in the valproic acid (VPA)–induced mouse model of autism. In addition, pentylenetetrazole (PTZ)-induced seizure was significantly attenuated by NaPB treatment in C57BL/6J and BTBR mice. These findings suggest that NaPB may provide a novel therapeutic approach for the treatment of patients with ASD.

https://link.springer.com/article/10.1007/s00213-021-05812-z

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate...

06/12/2023

SODIUM PHENYLBUTYRATE AND ADRENOLEUKODYSTROPHY (ALD) RESEARCH

Sodium phenylbutyrate ALD research studies have shown promising results for adrenoleukodystrophy treatment.

Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 18,000 people. It most severely affects boys and men and knows no racial, ethnic, or geographic barriers. This brain disorder destroys myelin, the protective sheath that surrounds the brain’s neurons. The nerve cells that allow us to think and to control our muscles.

The most devastating form of ALD appears in childhood, generally between the ages of four and ten years old. Normal, healthy boys suddenly begin to regress. At first, they simply show behavioral problems, such as withdrawal or difficulty concentrating. Gradually, as the disease ravages their brain, their symptoms grow worse, including blindness and deafness, seizures, loss of muscle control, and progressive dementia. This relentless downward spiral leads to either death or permanent disability, usually within 2 to 5 years from diagnosis.

https://sodiumphenylbutyrate.com/adrenoleukodystrophy-treatment/

05/19/2023

MEDICAL FACILITIES USING SODIUM PHENYLBUTYRATE

Across the world, there are numerous medical and research facilities using sodium phenylbutyrate in clinical studies.

Clinical studies are in progress around the world using sodium phenylbutyrate to discover new things about a multitude of diseases and potential treatments. This includes sodium phenylbutyrate ALS studies, sodium phenylbutyrate cancer studies, and research into innovative new sodium phenylbutyrate uses.

Below is a list of medical facilities that are using or have used sodium phenylbutyrate in clinical research. Some facilities may be using related sodium phenylbutyrate formulations like triButyrate, phenylbutyric acid, sodium phenylbutyrate iv, or AMX0035.

United States

Auburn University
Baylor College of Medicine
Boston College
Children’s Hospital of Philadelphia
Cincinnati Children’s Hospital
Columbia University
Cornell
Harvard School of Public Health
Harvard University
Henderson Research Center
Thomas Jefferson University
Johns Hopkins
Mayo Foundation
North Texas Eye Institute
North Texas Health Center
Temple University Texas Southern University
University of Albany
University of Arkansas
University of CA – Irvine
University of CA – SF
University of Chicago
University of Colorado Health Science Center
University of Iowa
University of Michigan
University of Missouri
University of Texas – MD Anderson
Utah State University
VA Medical Center, Boston
Vanderbilt University Medical Center

International

Copenhagen University, Denmark
Hospital de Clínicas de Porto Alegre, Brazil
Karolinska Institute, Sweden
McGill University, Canada
McMaster University, Canada
Oxford University, UK
University of Alberta, Canada
University of BC, Canada
University of Madrid, Spain
University of Montreal, Canada
University of Munich, Germany

https://sodiumphenylbutyrate.com/medical-facilities/

04/26/2023

CLINICAL USE OF SODIUM PHENYLBUTYRATE

Sodium phenylbutyrate is contributing to the global health landscape through emerging research and clinical trials.

Refer to the clinical use of sodium phenylbutyrate in research and trial studies for the treatment of disorders such as cancer, ALS, ALD, and diabetes.

Copies of clinical trials are available upon request for these indications:
Addiction
Adrenoleukodystrophy (ALD)
Aging
Alzheimer’s disease
Amyotrophic lateral sclerosis (ALS)
Bladder dysfunction
Blood
Cancer
Cardiac injury
Cerebral ischemic injury
Cystic fibrosis
Diabetes
Endoplasmic reticulum stress
Epilepsy
Eye
Familial hypercholesterolemia
Spinal muscular atrophy
Urea cycle disorder/ornithine transcarbamylase deficiency
Huntington’s disease
Ischemic spinal cord damage
Kidney
Leucine metabolism
Lipoprotein receptor
Liver
Lung/abca3 defects
Maple syrup urine disease
Multiple sclerosis (MS)
Muscular Dystrophy
Obesity
Parkinson’s disease
Phenylketonuria
Rheumatoid arthritis
Schizophrenia
Sickle cell anemia, thalassemia, and Cooley’s anemia
Miscellaneous research and articles

https://sodiumphenylbutyrate.com/clinical-use-sodium-phenylbutyrate/

04/06/2023

SODIUM 4-PHENYLBUTYRATE REDUCES OCULAR HYPERTENSION BY DEGRADING EXTRACELLULAR MATRIX DEPOSITION VIA ACTIVATION OF MMP9

From: North Texas Eye Research Institute

Abstract
Ocular hypertension (OHT) is a serious adverse effect of the widely prescribed glucocorticoid (GC) therapy and, if left undiagnosed, it can lead to glaucoma and complete blindness. Previously, we have shown that the small chemical chaperone, sodium-4-phenylbutyrate (PBA), rescues GC-induced OHT by reducing ocular endoplasmic reticulum (ER) stress. However, the exact mechanism of how PBA rescues GC-induced OHT is not completely understood. The trabecular meshwork (TM) is a filter-like specialized contractile tissue consisting of TM cells embedded within extracellular matrix (ECM) that controls intraocular pressure (IOP) by constantly regulating aqueous humor (AH) outflow. Induction of abnormal ECM deposition in TM is a hallmark of GC-induced OHT. Here, we investigated whether PBA reduces GC-induced OHT by degrading abnormal ECM deposition in TM using mouse model of GC-induced OHT, ex vivo cultured human TM tissues and primary human TM cells. We show that topical ocular eye drops of PBA (1%) significantly lowers elevated IOP in mouse model of GC-induced OHT. Importantly, PBA prevents synthesis and deposition of GC-induced ECM in TM. We report for the first time that PBA can degrade existing abnormal ECM in normal human TM cells/tissues by inducing matrix metalloproteinase (MMP)9 expression and activity. Furthermore, inhibition of MMPs activity by chemical-inhibitor (minocycline) abrogated PBA’s effect on ECM reduction and its associated ER stress. Our study indicates a non-chaperone activity of PBA via activation of MMP9 that degrades abnormal ECM accumulation in TM.

https://www.mdpi.com/1422-0067/22/18/10095

Ocular hypertension (OHT) is a serious adverse effect of the widely prescribed glucocorticoid (GC) therapy and, if left undiagnosed, it can lead to glaucoma and complete blindness. Previously, we have shown that the small chemical chaperone, sodium-4-phenylbutyrate (PBA), rescues GC-induced OHT by r...