Why is dopamine reduction therapy for Parkinson's disease so exciting?

In the 1880s, Robert Koch (and his assistant Friedrich Loeffler) proposed criteria to prove a specific microorganism caused a specific infectious disease. The approach is very logical, requiring that a microorganism is identified that is present in the disease and that produces the same disease when introduced into another host. Unfortunately we all understand this logic.

There are no such definitions for the evidence required to prove a cause of most chronic diseases. It's why we read day after day about a breakthrough identifying the cause of a disease, only to learn that the claim is made based on some correlation but without showing cause.

I've learned about drug development from the best. And I've been a disciplined student, reviewing FDA briefing materials on a wide range of drugs over the past 30+ years. And so here is my version of Drug Development Postulates to establish criteria that establish a causal relationship between abnormalities and human disease.

1. Identify a target for treatment, where a target is an abnormality that can be measured in people.

2. Identify existing, validated pre-clinical models with that abnormality.

3. Demonstrate that reversing that abnormality reverses pathology of the disease in pre-clinical models (and the more models the more persuasive the findings).

4. Validate the therapy's safety and effectiveness in people.

Data show that the first 3 of these Drug Development Postulates are satisfied by dopamine reduction therapy with RB-190. (1) We published the first study to report the intracellular (cytosolic) levels of dopamine in dopaminergic neurons from people with Parkinson's. The levels are high. And other studies support these findings. (2) We identified nine pre-clinical models of Parkinson's none of which report dopamine is deficient. These models were studied by other, independent labs, without Right Brain providing funding, editing the publications or influencing the results in any way. (3) In each of these 9 models, RB-190 was shown to reverse pathology.

So the next step is testing postulate #4: to show whether dopamine reduction is a safe and effective therapy for Parkinson's.

When we conduct the first clinical trial (Phase 2A) and show that reducing dopamine does not worsen clinical condition, we will have shown that Parkinson's is not a disease where dopamine deficiency is the cause.

The scientists will conclude we've satisfied the criteria to show that dopamine excess is the cause.

Patients, their families and clinicians will conclude that we need to pour resources into further development of dopamine reduction therapy for PD in order to advance the therapy to market.