#65: Dr Howard Weiner, MD, Understanding the Neuroinflammatory diseases: MS, Alzheimer's, Parkinson's, ALS & Glioblastoma

Dr Howard Weiner has been evaluating neuroinflammatory diseases for over forty years now. Multiple sclerosis (MS) is his main target, but in the show today, you’ll hear how comparing the causes and courses of Alzheimer’s, Parkinson’s, ALS (Amyotrophic lateral sclerosis), and glioblastoma can tremendously deepen our insight into all of these neuroinflammatory conditions together. Dr Weiner is a story-teller (and film maker! ‘What is Life? The Movie”) who starts with a description of the four types of cells that make the brain into the brain: neurons, oligodendrocytes, astrocytes, and microglia. Then it’s on to the details: MS is white blood cells entering the brain triggering inflammation, while abnormal protein accumulation is the hallmark for Alzheimer’s (amyloid & Tau proteins), Parkinson’s (alpha-synuclein in the dopaminergic areas), and ALS (TP protein and others). As we wind our way through the immune system, Dr Weiner shares their surprise at finding MS has a pathologic B-cell component. Antibody-oriented diseases can be addressed with what’s called monoclonal antibody drugs, many of which are used for MS therapy (and 1000’s of other ‘mab’ drugs for other autoimmune diseases). We then turn to the concept of using vaccines for autoimmune conditions. By priming the immune system, we can change the way it reacts to threat & inflammation- these are being considered for both Alzheimer’s (Protollin from bacteria) & MS (stimulates T cells to dampen microglial activity). This is followed with discussion about the links between the brain & the gut/ microbiome and the gut/brain axis impact on neurological disease. He notes even certain cancer therapies that work better or worse dependent on the microbiome. He lays out the challenges of large-scale trials which often don’t yield game-changing success stories but can still be of great value on the secondary analysis to tease apart the patients that did gain benefit to then work backwards judging if other similar sub-set patients could be served by said intervention. This serves for some of the upcoming potential treatments in current trials including aspects of xenon gas, 40Hz flickering light for Alzheimer’s (https://www.alz.life/), ibudilast, inhaled cromolyn to control microglial inflammation, and/or stem cell injections into the spinal cord. Dr Weiner ends by recognizing the frustration and fear that these neuroinflammatory conditions can inspire, but emphasizes the importance of having hope and the incredible gains we’ve made, which will continue, especially in treating MS, over the past 40+ years.

Resources:

· Dr Weiner’s Lab website: https://weinerlab.bwh.harvard.edu/?page_id=154

· Book: “The Brain Under Siege, solving the mystery of brain disease, and how scientists are following the clues to a cure” by Dr Howard Weiner, MD (2021)

· Book: Curing MS: How Science is Solving the Mystery of Multiple sclerosis (2005)

· Movie: What is Life- the Move: https://www.youtube.com/watch?v=MxUFD1UsCpc