Valproic Acid – benefits eye disease!
A commonly used anticonvulsant drug in low dosages may help patients with macular degeneration!
Dr. Kaushal, fUniversity of Massachusetts Medical School, also shared with me his research on a commonly used anticonvulsant drug in low dosages that has shown positive benefits in patients with macular degeneration. He has been giving his macular degeneration patients low dosages of Valproic Acid and has observed that many of them do not need a second injection of Lucentis or Avastin.
This drug has several documented affects:
1-It is an anti apoptotic agent( helps reduced cell death)
2-It decreases inflammatory cytokinase ( helps reduce cell inflammation)
3-Reduces cytolysis ( cell destruction)
4-Increases pump efficiency of the retinal Pigment epithelium ( a very important layer in the retina and felt to be the location of beginning macular degneration)
What does this mean? According to Dr Kaushal this drug should improve the outcome of microcurrent treatments! It is interesting since this drug is also used in bipolar disorders and has a calming effect. Dr. Kaushal and I discussed that perhaps a mechanism of this drug is to help balance the autonomic nervous system and enable the body to heal. This is very exciting and I am investigating this drug as an addition to improve the outcomes of patients who receiving microcurrent.
Here are some research articles on Valproic Acid
Scientists from the RIKEN Research Institute and Kyoto University in Japan are reporting that Valproic Acid stimulated a specific biochemical pathway which achieved greater retinal regeneration in a rat model.
Normally retinal support cells called Muller glia could de-differentiate to assume a neuronal fate, but the level of regeneration via this mechanism was very low, occurring in just a few cells. But the new study, published recently in the Journal of Neuroscience, indicates that retinal cell regeneration in an in vitro model of retinal damage can be increased by as much as twenty-fold!” Furthermore, the retinal neurons were regenerated all over the retina.”The regenerated cells migrated to the outer nuclear layer of the retina, where, in the presence of retinoic acid (a form of vitamin A) or valproic acid, the team observed differentiation into rod photoreceptor cells.
Valproic Acid–Mediated Neuroprotection and Regeneration in Injured Retinal Ganglion Cells Julia Biermannand et al.Lagrèze1 From the 1University Eye Hospital Freiburg,Germany;
In this article retinal and axonal damage was measured after a crush injury of the opic nerve in mice. VPA provided neuro-protection and axonal regrowth after ONC. Alterations were observed in several pathways; however, the precise mechanism of VPA-mediated protection is not yet fully understood.
Valproic acid shown to halt vision loss in patients with retinitis pigmentosa
Published: Wednesday, July 21, 2010 – 15:22 in Health & Medicine
Researchers at the University of Massachusetts Medical School (UMMS) believe they may have found a new treatment for retinitis pigmentosa (RP), a severe neurodegenerative disease of the retina that ultimately results in blindness. One of the more common retinal degenerative diseases, RP is caused by the death of photoreceptor cells and affects 1 in 4,000 people in the United States. RP typically manifests in young adulthood as night blindness or a loss of peripheral vision and in many cases progresses to legal blindness by age 40. In the July 20 online edition of the British Journal of Ophthalmology, Shalesh Kaushal, MD, PhD, chair of ophthalmology and associate professor of ophthalmology and cell biology at UMMS, and his team, describe a potential new therapeutic link between valproic acid and RP, which could have tremendous benefits for patients suffering from the disease. In a retrospective study, valproic acid—approved by the FDA to reduce seizures, treat migraines and manage bipolar disorder—appeared to have an effect in halting vision loss in patients with RP and in many cases resulted in an improved field of vision. Results from this study, in conjunction with prior in vitro data, suggest valproic acid may be an effective treatment for photoreceptor loss associated with RP.
UMass Medical School will be the coordinating site for a $2.1 million, three-year clinical trial funded by the Foundation Fighting Blindness/National Neurovision Research Institute quantifying the potential of valproic acid as a treatment for RP. The clinical trials will build upon Kaushal’s work in the retrospective study in which patients were treated off-label with doses of valproic acid ranging from 500mg to 750mg per day over the course of two to six months. Treated at a time when patients normally experience rapid vision loss as a result of RP, five of the seven patients in the study experienced improvement in their field of vision.
“Inflammation and cell death are key components of RP,” said Kaushal. “It appears the valproic acid protects photoreceptor cells from this. If our observations can be further substantiated by randomized clinical trials then low dose valproic acid could have tremendous potential to help the thousands of people suffering from RP.”
To date, discovery of a treatment for RP has been complicated by the fact that more than 40 different genes have been linked to the disease, making many interventions impractical or impossible; as a result, the disease remains largely untreated for an estimated 100,000 patients in the U.S. Most RP therapies currently being investigated focus on nutritional supplementation, vitamin A supplementation, light reduction or gene therapy.
Dr. Kaushal and colleagues, having previously demonstrated the use of the small molecule, retinoid, as a pharmacological agent capable of increasing the yield of properly folded RP rhodopsins, began screening other small molecules for similar attributes. Because of its already known qualities as a potent inhibitor of the inflammatory response pathway and cell death, valproic acid was believed to have a unique profile making it a potential candidate as a retinal disease treatment.
“Traditionally, moving a new scientific discovery from the bench to the patient requires a significant investment of time and resources,” said Kaushal. “Repurposing drugs already approved by the FDA and which have been shown to be safe, such as valproic acid, is an economical and time-efficient way to quickly bring new treatments to patients.”
“The Foundation Fighting Blindness is delighted to be moving Dr. Kaushal’s outstanding work with valproic acid into our clinical trial network, because the drug has the potential to preserve vision for thousands of people affected by retinal diseases,” said Steve Bramer, Ph.D., chief drug development officer, National Neurovision Research Institute, a clinical support arm of the Foundation Fighting Blindness. “It’s an exciting research collaboration for us, because of the drug’s potential, and the knowledge and expertise Dr. Kaushal and the University of Massachusetts Medical School bring to the clinical study.”