Neurodegenerative Diseases: Scientific Advances That Are Transforming Their Treatment

There is a very specific moment in many neurodegenerative diseases when something changes, yet no one perceives it. It is not an obvious symptom or a clear functional loss, but a silent imbalance at the cellular level. By the time the first clinical signs appear, this process has been underway for years, sometimes decades.

For a long time, research has been forced to work within this gap: detecting damage only once it was visible and intervening when the disease was already advanced. The ability to identify biological changes before symptoms emerge, together with a more detailed understanding of the underlying cellular mechanisms, is driving a shift that is not only conceptual. It also opens the door to earlier, more precise, and potentially more impactful interventions.

Neurological disorders are currently one of the leading causes of disability and mortality worldwide. It is estimated that more than 55 million people are living with dementia globally, a figure that could double in the coming decades. At the same time, the healthcare and economic burden associated with conditions such as Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and hereditary ataxias continues to rise in increasingly aging societies.

A heterogeneous group with shared biological foundations

The term “neurodegenerative diseases” encompasses a wide range of conditions that differ significantly from one another, yet share a common biological pattern: progressive neuronal loss, accumulation of misfolded proteins, and gradual deterioration of the mechanisms that maintain cellular homeostasis. What varies from one disease to another is less the nature of the process than its location, its progression rate, and the functions it ultimately affects.

Among the most studied are several conditions that, despite being well known, still pose major unanswered questions:

• Alzheimer’s disease, the most common form of dementia, initially presents as memory loss and progressive cognitive decline. Biologically, it is associated with the accumulation of beta-amyloid and tau proteins, which disrupt neuronal communication and ultimately compromise cell survival.
• Parkinson’s disease, characterized by loss of motor control, tremors, and muscle rigidity. In this case, the problem originates from the degeneration of dopamine-producing neurons, along with the accumulation of alpha-synuclein in structures known as Lewy bodies.
• Amyotrophic lateral sclerosis (ALS), a particularly aggressive disease that affects motor neurons responsible for voluntary movement. As these neurons degenerate, patients progressively lose the ability to move, speak, and breathe, while cognitive functions often remain intact in many stages of the disease.
• Prion diseases, much rarer but extremely rapid in progression, in which a misfolded protein triggers a chain reaction that alters healthy proteins, leading to severe neurological deterioration in a short period of time.

For years, research focused on these aggregated proteins as the main cause of neuronal damage. However, current knowledge points to a more complex scenario. Today, it is understood that multiple biological processes converge in these diseases, including mitochondrial dysfunction, alterations in energy metabolism, failures in cellular degradation systems, neuroinflammation, and genetic predisposition. This more integrated view, supported by recent studies, has shifted the focus from a single trigger to interconnected pathological networks, where multiple factors interact and reinforce one another.

From symptom to molecular mechanism

En In the study of neurodegenerative diseases, the clinical analysis of symptoms has long been the foundation for understanding and diagnosing these conditions. In recent years, this approach has been complemented by greater attention to the biological processes that precede those symptoms, expanding the ability to characterize disease in earlier stages.

In Alzheimer’s disease, for example, the criteria established by the Alzheimer’s Association now incorporate measurable biological indicators, such as beta-amyloid and tau accumulation, detectable through PET imaging or cerebrospinal fluid analysis even before symptoms appear. This shift enables identification of the disease at much earlier stages.

This approach has directly influenced therapeutic development. Antibodies targeting beta-amyloid protein, although their clinical results remain under debate, reflect an effort to intervene in the underlying mechanism rather than merely treating symptoms.

At the same time, genetic sequencing has made it possible to identify molecular subtypes in diseases such as ALS, as well as to classify the disease as sporadic (90–95% of cases) or familial (5–10%). Mutations in genes such as SOD1 have opened the door to targeted therapies, such as antisense oligonucleotides, designed to reduce the production of altered proteins. These strategies represent some of the first advances toward precision medicine in neurodegeneration.

ALS: a paradigm of scientific urgency

La Amyotrophic lateral sclerosis occupies a particular place within this landscape. It is a rare but devastating disease, with an average survival of three to five years after diagnosis, which typically occurs when symptoms have already been present for a long time. It selectively affects cortical and spinal motor neurons, leading to progressive muscle weakness and respiratory failure.

For years, therapeutic options were limited and had modest impact. However, the identification of genetic subtypes and a deeper understanding of the underlying cellular processes are reshaping research in this field. International initiatives such as the Project MinE consortium have generated large-scale genomic datasets to accelerate the discovery of therapeutic targets.

ALS illustrates how our understanding of these diseases is evolving. It is increasingly viewed not as a single uniform entity, but as a set of molecular alterations converging into a common clinical phenotype. This deeper biological characterization enables more targeted therapeutic strategies, although it also introduces new challenges in clinical trial design, which must adapt to greater diversity in patient profiles.

Beyond neurons: the role of the cellular environment

Another important shift is the recognition of the role of non-neuronal cells. The activation of microglia and astrocytes, alterations in the blood–brain barrier, and the involvement of the peripheral immune system are now understood as part of the pathological landscape. Neurodegeneration is increasingly seen as a multicellular process.

This broader perspective has driven the search for therapies that modulate inflammation, metabolism, or intercellular communication. The challenge lies in intervening without disrupting essential physiological functions, which requires a nuanced understanding of the biological balances involved.

Molefy Pharma and the search for new targets

In this context, biotech spin-offs are playing an increasingly important role in translating scientific knowledge into concrete therapeutic solutions. At ARQUIMEA, this commitment is embodied in Molefy Pharma, a company founded in 2024 with a clear objective: to develop therapies capable of changing the course of neurodegenerative diseases, with a primary focus on amyotrophic lateral sclerosis (ALS).

Unlike more traditional approaches, Molefy Pharma focuses its research on identifying new molecular targets that allow intervention in the cellular processes driving the disease. Its main line of work centers on the development of AP-2, a small molecule designed to restore cellular balance by regulating a key kinase involved in the homeostasis of the TDP-43 protein, whose abnormal accumulation is present in the vast majority of ALS cases.

This approach does not aim merely to slow disease progression, but to go a step further: to intervene in the mechanisms that originate the disease with the goal of reversing cellular dysfunction. Data obtained from patient-derived cellular models and preclinical animal studies show a promising profile in terms of both efficacy and safety, positioning these strategies as highly relevant within current therapeutic development.

The work of Molefy Pharma reflects a broader trend in the field: moving toward therapies that act on specific biological processes, integrating molecular knowledge with pharmaceutical development. In diseases such as ALS, where clinical urgency is particularly high, this approach not only expands the range of available options but also introduces a different expectation, the possibility of intervening more directly at the root of the disease.

In this sense, research in neurodegeneration is no longer limited to describing deterioration, but to understanding it with sufficient precision to attempt to modify it. It is at this intersection between fundamental science and applied development where initiatives such as Molefy Pharma find their purpose, providing new tools to a field that, until recently, offered very few real therapeutic alternatives.