The cause of MS is still unknown. It is considered a disease of the immune system which attacks the Myelin which is the protective cover for central nervous system (CNS) cells. Most current therapies work by suppressing or redirecting the immune response or by attempting to mitigate myelin injury, not targeting neurons per se. These therapies only marginally or temporarily reduce MS symptoms for some patients and do not eliminate MS relapses/attacks. Until recently focus on the immune system has guided much of the MS research agenda.
New evidence suggests oxidative stress, which may result from inflammation or trauma, plays a critical role in demyelinating and damaging axons in MS. But to date free radical scavengers have been ineffective at preventing or treating this disease. Neuro Vigor has developed compelling evidence to implicate a specific neuro toxin, Acrolein, a product of lipid peroxidation, and both a potent pro-inflammatory agent and pro-oxidative stress aldehyde, as a causal factor in MS pathogenesis. Acrolein has demonstrated high direct toxicity to myelin and neurons; pronounced ability to perpetuate oxidative stress and inflammation; extended presence within biological systems; and elevated concentration in both human patients with MS and animal models of MS where mitigation of myelin damage by acrolein scavengers has been observed.
Dr. Riyi Shi, Neuro Vigor’s co-founder, has demonstrated a conspicuous beneficial effect of Acrolein-scavenging in a primary-progressive (PP) animal model of MS which is characterized by steady worsening of neurologic functioning. His pre-clinical work verified that the generic hypertensive drug Hydralazine:
- Reduces Acrolein levels in MS animal models by 30% in tissue and 70% in urine
- Delays onset of MS symptoms in animals by 33% (NOTE: 33% of the animals; 33% in days and if so over what period of time (how many days) ??)
- Delays and lowers MS symptom severity and reduces nerve membrane damage in animals
- Improves motor behaviors after onset of MS symptoms in animal models by 30%
- Enters brain and spinal cord rapidly–reaches therapeutic level in less than 2 hours.
- Low dosage generates therapeutic results/positive changes.
Neuro Vigor believes Hydralazine therapy will become a preferred MS treatment monitored by a Neuro Vigor companion diagnostic. For MS patients MS Hydralazine therapy will address: 1) treatment earlier in the disease progression including Acrolein reduction as a means to delay onset for patients who demonstrate a genetic MS proclivity or Acrolien sensitivity; 2) treatment to replace drugs which generate most severe patient side effects; 3) treatment with positive results, e.g. reducing the severity of relapses and frequency of attacks while increasing the healing re-myelination process; 4) treatment which delays disease progression, e.g. from relapsing remitting to progressive.
The market for MS drugs is $14 billion annually, with $8.5 billion of that in the United States. More than 400,000 people in the U.S. have been diagnosed with MS, while worldwide the number exceeds 2.1 million people.
Demand for MS drugs which are more effective, affordable, and have fewer side effects is significant. As a result, Dr. Shi has received scores of messages from desperate MS patients and their families seeking relief of their symptoms. An innovative path for MS treatment involving the reduction of Acrolein offers patients the potential for significant disease management relief with fewer and less severe side effects.
In terms of the importance of diagnostics, MS is a very complex and heterogeneous disease and therefore is difficult to diagnose accurately. Today, MS diagnosis is pieced together from clinical findings supported by ancillary tests, such as magnetic resonance imaging (MRI) of the brain and spinal cord augmented by cerebrospinal fluid and blood serum testing (Oligo Banding Assays).
Offering Acrolein as a diagnostic marker for MS from either a blood or urine patient sample will require clinical validation with MS patients. Acrolein may also be combined with other markers in a diagnostic assay to provide a more comprehensive approach for MS screening, diagnosis, and prognosis of relapse/remitting attacks, e.g. CIS – Clinically Isolated Syndrome. Offering a companion diagnostic for regulating Hydralazine therapy monitoring for CIS will provide significant relief to MS patients worldwide.
Neuro Vigor is now engaged in advanced pre-clinical work to further strengthen the business case for the positive impact of Hydalazine in relapsing remitting MS animal models and as a diagnostic indicator of relapses, disease progression and therapy effectiveness.