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The Spark #5 2025 Year-End Momentum

By S —

A “living drug” that makes L-DOPA in the gut moves toward human trials, gene therapies inch closer to the clinic, and new devices promise more precise brain targeting with less damage. Early-stage data also boost confidence in mitochondria-focused and GLP-1–based approaches.

The brief

Fresh sparks from the world of Parkinson’s:

  • Researchers have engineered a probiotic version of E. coli Nissle that produces L-DOPA directly in the gut, offering a steadier, pill-free way to manage Parkinson’s symptoms. Unlike standard L-DOPA, which causes dopamine spikes and dips that can trigger dyskinesia, this “living drug” delivers a continuous stream of the medication, improving motor control in preclinical models. The approach is now ready for human trials and could open the door to similar microbiome-based treatments for other neurological and gut-related disorders.
  • Alector plans to seek FDA approval for its Parkinson’s therapy AL050 in 2027; the therapy delivers a functional GCase enzyme to the brain using the company’s ABC platform, which helps treatments cross the blood-brain barrier. AL050 targets patients with GBA1 mutations, a common genetic driver of Parkinson’s, and preclinical data show improved enzyme activity and reduced toxic buildup. Alector is also advancing ADP062-ABC, aimed at lowering alpha-synuclein accumulation.
  • Virginia Tech researchers are developing ultra-thin implantable fibers that combine electrical, optical, and drug-delivery capabilities to study deep brain regions and precisely target malfunctioning circuits. The tech could identify seizure starting points, deliver drugs directly into the hippocampus to slow Alzheimer’s progression, and enable smaller, more programmable deep-brain-stimulation devices for Parkinson’s—offering more effective therapies with less damage to the brain.
  • GEN reported new Phase 1 data for SUL-238, a first-in-class, mitochondria-targeted drug for Alzheimer’s and other neurodegenerative diseases, showing it’s safe, well-tolerated, and reaches the cerebrospinal fluid at strong levels in healthy older adults. The 14-day, multiple-dose study across two cohorts found no meaningful safety issues, only mild side effects comparable to placebo, and rapid absorption with a short half-life. With solid pharmacokinetics and clear brain penetration, SUL-238 looks like a promising candidate as it moves toward next-stage trials for Alzheimer’s, Parkinson’s, and related conditions.
  • Rethinking dopamine’s job in movement. A McGill-led study argues dopamine may act less like a “gas pedal” for movement and more like a permissive “baseline enabler,” which could influence how scientists think about symptom control vs. restoring foundational dopaminergic tone.
  • Oral Semaglutide as a potential disease-modifying candidate: trial protocol published. BMJ Open published the protocol for the MOST-ABLE randomized, double-blind study testing oral semaglutide tablets in Parkinson’s—useful for tracking endpoints, dose strategy, and timelines as GLP-1 interest continues.

Paper Under Review

Alpha-synuclein amyloids catalyze the degradation of ATP and other nucleotides
This paper proposes a previously unrecognized gain-of-function for alpha-synuclein amyloids affecting ATP/nucleotide metabolism—potentially connecting protein aggregation directly to cellular energy failure pathways.

The Human Spark

Jimmy Choi is an American endurance athlete, Parkinson’s advocate, and motivational speaker. Diagnosed with young-onset Parkinson’s disease at age 27, he transformed his life through exercise, advocacy, and competitive sport. He is widely known for his multiple appearances on NBC’s American Ninja Warrior and for raising awareness and funds for Parkinson’s research.

Spark tip

Build a “PD one-pager” for emergencies + hospital visits. Keep a single page with: exact meds + doses, strict timing, what happens if doses are late, your neurologist contact, allergies, swallowing risks. It’s a tiny prep step that can prevent outsized setbacks when you’re stressed, traveling, or admitted unexpectedly.

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Disclaimer: SparkPD is for informational purposes only and not medical advice.