Fibroblast Growth Factor 1 (FGF-1), a naturally occurring protein, is being studied for its potential role in Parkinson’s Disease (PD), a progressive neurological disorder. This article explores how FGF-1’s regenerative properties might offer new therapeutic avenues for PD.
FGF-1’s Role in Brain Health
FGF-1 is a signaling protein involved in the development, maintenance, and repair processes of the nervous system. It influences interactions between myelinating cells, axons, astrocytes, microglia, and neurons.
FGF-1 exhibits neurotrophic properties, supporting the survival and differentiation of neurons. It stimulates neuron survival, differentiation, and growth, especially after injury. FGF-1 and its receptors, particularly FGF receptor 1 (FGFR1), are widely distributed in the brain, including in neurons, astrocytes, and radial glia.
Parkinson’s Disease and Neurodegeneration
Parkinson’s Disease is a progressive neurodegenerative disorder marked by the gradual loss of dopamine-producing neurons in the substantia nigra. This leads to dopamine deficiency in the striatum, affecting smooth movement. By the time symptoms appear, 60% to 80% or more of these cells may already be lost.
A hallmark of Parkinson’s Disease is the presence of Lewy bodies, which are abnormal clumps of protein, predominantly made up of misfolded alpha-synuclein, found within affected brain cells. The accumulation of alpha-synuclein is thought to contribute to the neurodegenerative process. The disease manifests with motor symptoms such as tremor, slowness of movement (bradykinesia), limb stiffness, and problems with gait and balance. Non-motor symptoms, including depression, anxiety, sleep disorders, and loss of smell, can also occur and sometimes precede motor symptoms by many years.
Investigating FGF-1 as a Therapeutic Strategy
FGF-1’s potential as a Parkinson’s Disease therapy comes from its diverse actions against the disease’s pathology. It has neuroprotective capacity, shielding existing neurons from damage. Preclinical studies show FGF-1 can protect dopaminergic neurons, preserving these vulnerable cells.
Beyond neuroprotection, FGF-1 is explored for its neurogenic properties, promoting new neuron growth. Studies suggest it can encourage stem cell differentiation into dopaminergic neurons, potentially replenishing lost cells in the substantia nigra. This regenerative capacity offers a promising avenue for addressing dopamine deficiency in PD.
FGF-1 also influences neuroinflammation, a recognized contributor to neuronal damage in Parkinson’s Disease. Activated microglia and infiltrating T cells are observed in the substantia nigra of PD patients, contributing to chronic inflammation. FGF-1 and its receptors play a role in modulating neuroinflammation, which could help reduce harmful inflammatory responses that accelerate neurodegeneration.
FGF-1’s potential to improve mitochondrial function is also under investigation. Mitochondrial dysfunction and oxidative stress contribute to nerve damage in Parkinson’s Disease. FGF-1 may help by inhibiting the transfer of stressed mitochondria to glial cells, impeding neuroinflammation and neurodegeneration. This multifaceted action suggests FGF-1 could address multiple pathways in PD progression.
Current Research and Future Directions
Research into FGF-1 for Parkinson’s Disease is currently in various stages, with promising results primarily emerging from preclinical (laboratory) studies. These studies, often conducted in mouse and monkey models of PD, have shown FGF-1 can lead to the regeneration of dopaminergic neurons and improvements in motor function. Such findings provide a scientific basis for exploring its potential in human trials.
Early-phase clinical trials are also underway to assess the safety and efficacy of FGF-1 in people with Parkinson’s Disease. For example, one company has initiated a Phase 1 clinical trial to evaluate intranasal FGF-1, a proprietary version of the protein administered through the nose to enhance its delivery to the brain. Initial reports from this ongoing study involving over 200 patients have indicated improvements in motor function within six months, with some patients showing a 54% improvement on average.
Despite these encouraging early results, translating FGF-1 research into a widely available treatment faces challenges. A hurdle for neurotrophic factors like FGF-1 is their macromolecular size, which can make it difficult for them to cross the blood-brain barrier and reach affected brain regions effectively. However, the intranasal delivery method being explored aims to overcome this barrier by directly introducing the medicine into the brain. Future research will focus on long-term safety and efficacy, optimal dosing, and understanding the full scope of FGF-1’s impact on PD progression.