The broad space of neurodegenerative diseases comprises hereditary and sporadic conditions that are characterized by progressive dysfunction and of the nervous system and, in most cases, by atrophy of the affected structures. The dementias (Alzheimer’s Disease, Lewy Body Dementia, etc), Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s Disease), Huntington’s Disease, the progressive forms of Multiple Sclerosis (MS) and the Mitochondrial Diseases [Friedreich’s Ataxia (FRDA), Leber’s Hereditary Optic Neuropathy (LHON), etc] are important examples. The annual global medical care costs of the dementias alone exceed $600 billion. Despite the extensive research efforts invested in the past, effective treatments for these diseases are lacking.

Oxidative stress is an important pathophysiological process associated with the development of the neurodegenerative diseases. Although its cause may differ between diseases, the end result is the same: the oxidative damage of proteins, nucleic acids and lipids in the CNS, that leads to neurological dysfunction. Antioxidant treatments constitute a promising approach, however the inadequate pharmacokinetics of many existing compounds and the need to administer high concentrations are currently significant barriers to bringing effective drugs to the market.

Opportunity

BVA-101, BVA-201, BVA-202 and BVA-203 are repurposed drugs with clear antioxidant activity and favorable pharmacokinetics, including bioavailability and blood-brain barrier permeability. All drugs are currently approved for chronic indications and have exhibited excellent safety profiles in many different target populations, including geriatric patients. Biovista has established the antioxidant effects of these drugs ex-vivo and has demonstrated their efficacy in cell-line and animal models of several neurodegenerative disorders.

Results To Date

Mitochondrial Diseases

The effects of BVA-202 and BVA-203 on FRDA and LHON have been demonstrated in primary human fibroblasts, obtained from patients suffering from these diseases. The cells have been subjected to a BSO-induced oxidative insult and the protective effects of BVA-202 and BVA-203 against this insult have been studied by an industry standard luminescence/fluorescence kit. Both drugs produced statistically significant and sizable results, and outperformed idebenone, a potent antioxidant approved for the treatment of FRDA.

In a similar setup, BVA-202 and BVA-203 protected YG8R FRDA mouse cells against an oxidative insult induced by BSO and iron (ferrous ammonium citrate). These results indicate that BVA-202 and BVA-203 are effective against a variety of sources of oxidative stress, which are relevant to different human neurodegenerative disorders.

Multiple Sclerosis

In MS permanent neurological disability accumulates as the disease progresses; the inflammatory processes that underlie the early relapsing-remitting phenotype are gradually replaced by neurodegeneration, which manifests as neuronal and axonal loss and leads to accumulating neurological dysfunction. Neurodegeneration is a hallmark feature of primary and secondary progressive MS.

BVA-201 caused a sizable reduction in the severity of MOG-induced Experimental Allergic Encephalomyelitis (EAE), a mouse model of progressive MS. At the same time it reduced the extent of the neurological damage in the animals’ spinal cords, as seen in H&E stained histology section, but not the infiltration of the CNS by inflammatory cells.

This indicates that the activity of BVA-201 in preventing white matter damage is not related to any anti-inflammatory effects; rather, BVA-201 protects the neurons directly.

  • Both BVA-201 and dexamethasone reduce the area of the animals’ spinal cords that is affected by the disease
  • Contrary to dexamethasone, BVA-201 does not reduce the number of penetrating inflammatory cells
  • Therefore, BVA-201 exerts a direct neuroprotective, rather than anti-inflammatory, effect

Similarly, BVA-101 caused a significant reduction of disease severity in the MOG-EAE model.

Conclusions

BVA-101, BVA-201, BVA-202 and BVA-203 comprise a series of compounds that target oxidative stress and have yielded positive results in a range of cellular and animal models of different neurodegenerative diseases. Together with their favorable pharmacokinetics and established safety profiles, these results are strong predictors of efficacy in the corresponding human conditions.

Intellectual Property

The use of BVA-101, BVA-201, BVA-202 and BVA-203 in the new indications is protected by international patent applications, most of which are currently in the national phase. The patent applications also cover administration in several different dose ranges, routes of administration, as well as a number of drug combinations.

Licensing Opportunity

Our business model is based on licensing and joint-venture agreements for the development of repurposed drugs. If you are interested in exploring licensing or joint development opportunities please contact us at bd{at}biovista.com.