Porosome Discovery Promises to Revolutionize Modern Medicine

The discovery of the ‘porosome’, the cell's secretory apparatus, has provided a platform for entry into a new era in drug development and therapy. The porosome has been isolated, its structure and composition determined, and it has been functionally reconstituted into live cells.

Many diseases, such as Cystic Fibrosis, Type I & Type II Diabetes, neurological disorders, immune disorders and various cancers, result from secretory defects in the porosome. These diseases can now be addressed by incorporating the native functional porosome machinery into diseased cells, or by using small molecules and nanobodies directed at porosome proteins, to modulate the cell's secretory activity and treat the disease.

Porosomes: Unveiling Cellular Communication

Life's essence resides within cells, and the average human body has an astounding 38 trillion cells – equal to a linear length that could encircle half the globe. Vitality hinges on cell communication, achieved through the secretion of chemical messages by specialized nanomachines on cell plasma membranes known as "porosomes".

These porosomes, composed of over 30 proteins, play a pivotal role. Research underscores that alterations in specific porosome proteins lead to secretory disorders and diseases like Cystic Fibrosis, Cancer, Diabetes, and neurological conditions. We are actively advancing development of drugs targeting these diseases.

Frontiers of Innovation: Porosome Therapeutics Transformative Approach

At the forefront of biopharmaceutical advancement, Porosome Therapeutics harnesses pioneering insights and state-of-the-art technologies. Our goal is to identify and create groundbreaking, patent-pending therapies that specifically target currently “undruggable” porosome proteins and lipids that have been implicated in a range of challenging conditions, including Cystic Fibrosis, Cancer, Alzheimer's, Diabetes, neurological disorders, digestive issues, and immune disorders.

By skillfully merging breakthrough discoveries and cutting-edge methodologies, we've embarked on a mission to revolutionize the treatment landscape for these intricate and hitherto elusive health challenges. Our focus is on bringing forth therapies that were once deemed unattainable, opening new avenues of hope for those affected by these conditions.

Revolutionizing Drug Discovery - The Porosome Platform
The landscape of drug discovery has undergone a remarkable transformation propelled by breakthroughs in genomics, gene-editing technologies, stem cell biology, patient-derived organoids, cryo-electron microscopy, synthetic biology, and AI-driven small molecule screening with image analysis. These advancements have redefined the way we approach the development of therapeutics.

However, despite these leaps, a significant challenge persists: approximately eighty-five percent (85%) of disease-causing proteins remain elusive, impervious to current therapeutic interventions. This substantial limitation has spurred the birth of our revolutionary platform, rooted in a pivotal discovery within cell biology – the porosome.

The porosome, a cellular secretory portal essential for intercellular communication, holds the key to overcoming this challenge. Recognized across the industry as a game-changing revelation, our platform shatters the constraints that have hindered progress in drug discovery. By tapping into the potential of the porosome, we are breaking free from the confines that have limited our ability to target critical disease-causing proteins. This marks a new era in drug discovery, one where even the most elusive targets become attainable, fostering hope for transformative therapies that were previously out of reach.

The Porosome Platform is a revolutionary approach that goes beyond the confines of traditional screening methods. With the Porosome Platform, we're equipped to:

  1. Uncover Crucial Targets: Venturing beyond conventional limits, we delve into the realm of functional protein and lipid targets involved in cell communication through secretion processes.
  2. Precision Target proteins that cause disease: Our capabilities extend to the realm of pinpoint precision, enabling us to identify small molecules that can intricately bind to even the most complex targets, including those traditionally deemed "undruggable".
  3. Unveil New Modalities for treatment of disease: The Porosome platform opens doors to the modulation of secretory functions, ushering in new possibilities to address challenges that have persisted for ages. This includes tackling conditions such as cancer, diabetes, neurological disorders, and other historically elusive health issues.

Pathway to Discovery through the Porosome Platform
Within our pursuit, we continually screen thousands of small molecules across the 30+ proteins in the porosome complex, notably within neurons and the endocrine and exocrine pancreas. This process identifies novel high-affinity pockets within target proteins of interest. Data from this screening informs the creation of innovative covalent small molecules precisely engaging crucial drug targets.

The effectiveness of these compounds, either alone or in synergistic formulations, is first assessed in silico by gauging their binding affinities to target porosome proteins and lipids. This is followed by analyses involving cell cultures, organoids, and animal studies, paving the way for clinical trials. Driven by our proprietary industrial-scale platform, Porosome Therapeutics redefines druggability, crafting medications pertinent to a spectrum of secretory disorders.

The platform consists of five interconnected components, each contributing to its potential for therapeutic applications and drug screening.

  1. Functional reconstitution of the porosome complex which has been achieved both in a lipid membrane (as demonstrated in a study published in Biophysical Journal in 2003;85(3):2035-43) and in live cells (as shown in research published in Endocrinology in 2016;157(1):54-60). These breakthroughs offer significant promise for therapeutic interventions and high-throughput drug screening.
  2. Tissue-specific porosome-targeted therapy which has the potential to revolutionize medicine development by enabling the creation of an unprecedented variety of medicines tailored to a wide spectrum of medical conditions.
  3. Development of tissue-specific medicines targeted to porosomes not only advances therapeutic precision but also significantly elevates drug safety. By concentrating on the porosome, these medicines aim to effectively mitigate toxicity, minimize associated side effects, and mitigate various risks across the entirety of our drug portfolio.
  4. The integration of nanobody-assisted drug delivery technology further enhances the platform's capabilities. This technology, highlighted in a publication in Micron in 2017;92:25-31, accelerates the creation of precision medicines for diverse medical indications. This innovation paves the way for breakthroughs in drug design and delivery.
  5. The platform is supported by a global collaborative research network that capitalizes on a wealth of intellectual resources. This network enables the acceleration of drug design and development by leveraging collective expertise, thereby enhancing accuracy, speed, and efficiency in the research process.

In addition to these core components, the platform also addresses the challenge of diseases caused by pathogen entry into cells through the plasma membrane. Researchers are actively engaged in the identification of small molecule drugs that regulate various transport functions at the cell membrane. This strategic approach aims to prevent the entry of pathogenic viruses and mitigate associated diseases.

Cystic Fibrosis

Today, the average life expectancy for people with CF who live to adulthood, is about 44 years (https://medlineplus.gov/ency/article/000107.htm).

Cystic Fibrosis arises from a protein dysfunction stemming from mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). This chloride channel governs mucus viscosity, notably in lung epithelial cells. While current treatments mainly address the malfunctioning CFTR protein, Porosome Therapeutics pioneers an alternative. By reintroducing a functional CFTR-associated porosome secretory complex into lung epithelial cells affected by CF, we aim to rectify the deficiency caused by the non-functional mutated CFTR.

This innovative approach offers a comprehensive, curative solution for CF treatment. It has the potential to substantially reduce morbidity, mortality, and enhance the quality of life for CF patients. Moreover, this novel approach could significantly decrease the need for lung transplants among CF patients.

Concurrently, Porosome Therapeutics’ complementary small molecule therapy, distinct from existing treatments, targets porosome-associated proteins interacting with the CFTR protein. Leveraging our proprietary precision drug targeting approach employing small molecule-associated nanobodies, this strategy holds promise for heightened effectiveness and minimal side effects. Depending on the state of the CF disease, both reconstitution and small molecule therapies can be applied.

Type 1 and Type 2 Diabetes

Porosome Therapeutics has developed an innovative proprietary approach to effectively address the insulin secretion defects in both Type 1 and Type 2 Diabetes. This solution-set centers on the beta cells (β-cells) responsible for insulin production within the disease context:

  1. Utilizing Fundamental Sub-Cellular Mechanisms: For the first time, we harness the pivotal sub-cellular secretory nanomachine directly relevant to diabetes—the porosome complex. This complex operates in conjunction with the water-transporting aquaporin (AQP) water channel, crucial for regulated insulin secretion from β-cells.
  2. Deploying Paradigm-Shifting Therapeutic Technology: Our revolutionary approach introduces a proprietary therapeutic technology that fundamentally "corrects" the manifestations of Type 1 Diabetes. We accomplish this by "incorporating" functional porosome machinery into pancreatic β-cells derived from stem cells. This groundbreaking step holds promise for a comprehensive and long-lasting correction of diabetes-related deficiencies.
  3. Porosome-Targeted Small Molecule Therapies: Our strategy extends to providing targeted small molecule therapies. These therapies are designed to restore the insulin-secreting and insulin-producing capabilities of diseased β-cells, effectively returning them to a state of functional normalcy.
  4. Collaborative Research on Human Islets: In tandem with leading investigators in the field, we conduct joint research focused on human islets. This collaborative effort allows us to tap into diverse expertise, enhancing the precision and impact of our approach.
Porosome Therapeutics has crafted a multi-faceted solution that addresses the intricate mechanics of insulin secretion within both Type 1 and Type 2 Diabetes. By leveraging cutting-edge research and collaborative efforts, we aim to revolutionize the treatment landscape for these prevalent and impactful conditions.

Lung Adenocarcinoma

Lung cancer stands as the foremost contributor to both mortality and morbidity on a global scale. Its predominant manifestation takes the form of adenocarcinomas. Notably, diverse lung cancers display deficiencies in secretory processes within lung epithelial cells. A prime illustration is mucinous adenocarcinoma, where the inability to properly secrete mucus results in the constriction of airways. This mirrors symptoms reminiscent of those found in cystic fibrosis (CF), including obstructive pneumonia due to the failure of efficient mucus drainage.

In response to this pressing challenge, Porosome Therapeutics has devised a comprehensive strategy. This multifaceted approach entails the utilization of small molecule drugs and nanobodies, both directed at the porosome proteome within lung epithelial cells. The primary aim of this strategy is to intervene in and enhance the intricate process of mucus secretion. By doing so, the goal is to potentially alleviate obstructive pneumonia and other distressing symptoms associated with lung cancer.

Diseases associated with defects in neuronal porosome proteins

Alzheimer's disease presents distinct alterations in neuronal porosome proteins, with noticeable shifts in protein levels. Specifically, levels of CNPase (2,3-cyclic nucleotide phosphodiesterase) and heat shock protein 70 (HSP70) increase, while dihydropyrimidinase-related protein-2 (DRP-2) levels decrease. Notably, within the neurons of Alzheimer's patients, there are significant reductions in the porosome proteins SNAP-25 and synaptophysin.

CNPase levels consistently decrease in the frontal and temporal cortex of individuals with Alzheimer's disease and Down's syndrome. Likewise, reduced CNPase levels are observed in the anterior frontal cortex of individuals with schizophrenia. Additionally, a genetic allele associated with lowered CNPase levels is linked to schizophrenia, implying a genetic factor at play.

Conversely, abnormal levels of SNAP-25 exhibit distinct correlations. Elevated SNAP-25 levels are linked to cognitive deficits, potentially contributing to impaired cognitive function. In contrast, the absence of SNAP-25 is associated with Huntington’s disease, emphasizing its role in neurodegenerative disorders.

The intricate interplay of these porosome proteins underscores their significance in the pathophysiology of diverse neurological disorders, shedding light on potential avenues for therapeutic interventions and genetic influences.

Porosome Therapeutics’ Porosome Platform harnesses the intricate mechanisms of cellular communication for revolutionary drug discovery. It is unlocking the potential of previously overlooked proteins and offering innovative solutions for a wide spectrum of health challenges.

CNPase (2,3-cyclic nucleotide phosphodiesterase)DRP-2 (Dihydropyrimidinase-related protein-2)
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