Drug repurposing is the process of identifying new therapeutic uses for approved or investigational drugs that were originally developed for other medical conditions. Since drug repurposing involves screening drugs that might already be approved or have a known safety profile, treatments can be developed more quickly and at a lower cost compared to the traditional drug development process.

The types and number of compounds in a screen will depend on the research model and screening approach being used. Perlara has access to many drug-repurposing libraries, ranging from 1,500 to as many as 8,500 compound libraries. The composition of each library is different, but will typically include a combination of approved drugs, drugs in various stages of clinical development, nutraceuticals, supplements, bioactives or tool compounds. Based on your specific requirements and budget, we'll recommend the most suitable compound library for your screen.

In most cases, if a compound is available for purchase and research purposes, it can be included in a screening service. We will work with you to determine the best way to incorporate this compound into the screening process to obtain the most meaningful results.

The duration of the drug repurposing process can vary widely based on several factors such as the research model being used, the screening approach, and the drug repurposing candidates identified. From our experience, this process can span anywhere from 3 months to several years. There are a series of conditions that need to be met in order to launch an initial clinical trial of a newly-identified repurposing medicine. The major components include the identification of (a) medicine(s) that are safe (or at least that have a favorable balance of risk and potential reward), a reasonable understanding of the biological mechanism by which the medicine might improve the patient’s condition, availability of the medicine(s) in a pharmaceutical-grade stock, and a supportive clinician or clinical team to prescribe the medicine (if necessary) and monitor the patient’s response. There are also sometimes project-specific challenges that your Cure Guide can help you navigate.

The results from drug repurposing screens provide information on how different compounds affect the phenotype of the disease model (e.g. growth in yeast), which helps us identify the most promising repurposing candidates for a disease. Specifically, they reveal which compounds improve the disease phenotype (referred to as rescuers) and which worsen it (referred to as sensitizers). Both categories of hits provide valuable insights into the underlying disease mechanisms and potential disease-modifying targets. Understanding the mechanisms of action of screen hits and considering the attributes of a drug (such as its approval status, route of administration and safety profile), help identify the most clinically actionable repurposing candidates for a disease.

Once hits have been identified from the screen, our goal is to advance safe and clinically actionable drug-repurposing candidates into the clinic as fast as possible. However, the specific pathway from a hit to the clinic can vary depending on the repurposing candidates discovered in the screen. For instance, if readily available nutraceuticals or supplements are identified in a screen, treatment may begin within days of receiving the screening results. Whereas if a repurposing candidate is an existing approved drug or is still in clinical development, additional follow-up experiments or patient studies may be required to understand how the drug is working and to assess its efficacy and safety in patients. With our extensive experience in translating discoveries from the lab to the clinic, we'll help devise and implement the best strategy for developing new treatments, guiding you every step of the way.

The applicability of drug repurposing data from one mutation to other mutations of the disease-causing gene may vary. Different mutations can alter the structure and function of the protein encoded by the disease-causing gene, potentially influencing how drugs interact with it, and each mutation can affect the disease's biological mechanisms differently. Therefore, while certain drugs may show promise in targeting one mutation, further validation across research models of different mutations may be necessary to fully understand their efficacy and applicability across various mutations causing the disease. While there is no guarantee that a drug that can improve the disease state of a particular mutation will translate to others, in our experience common rescue mechanisms often exist, and there are factors that make this more likely. If different mutations have a similar pathological mechanism (i.e. loss-of-function, haploinsufficiency, dominant negative, gain-of-function, etc.), the likelihood that a particular drug candidate will translate across these mutations is higher. Your Cure Guide can help you understand the pathological mechanism of your mutation and ways to experimentally validate which hits from your screen will translate more broadly across different mutations.

Any data generated by research conducted or contracted by Perlara fully belongs to the client.

Perlara believes in the principles of open science and transparency. We frequently publish the latest discoveries from our partnerships with rare disease families and foundations on our Substack. We prioritize the sharing of de-identified results, to protect our clients and collaborators' intellectual property.

A disease model is a tool that scientists use to mimic the characteristics of a particular disease in a controlled environment. In the context of our research on rare genetic diseases, these models can be organisms, such as yeast or fruit flies, or cells such as fibroblasts or iPSCs, engineered to exhibit features of the disease. We call these models “patient avatars”. By studying these models, we gain insights into the underlying mechanisms of the disease and explore potential treatments.

The simplest model is yeast. Maintaining a high degree of similarity between the yeast genome and the human genome, allows us to rapidly evaluate the effect of many drugs. However, there are cases in which a yeast model is not a suitable model for a specific disorder. In these cases, we would opt for a different model, which mirrors the disease better. Drosophila melanogaster, commonly known as the fruit fly, is an exceptional model for studying human diseases. Beyond genetic similarity, the fly possesses sophisticated and complex systems, faithfully mimicking the functions of the mammalian heart, kidneys, gut, lungs, and nervous system. This versatility makes the fruit fly a valuable tool in disease research I nduced Pluripotent Stem Cells (iPSCs) can be precisely guided to differentiate into specialized tissues such as cardiomyocytes and neurons. They have the same genetic background as individuals affected by a particular disease. This allows us to precisely identify potential treatments tailored to specific disease variants.

Induced Pluripotent Stem Cells (iPSCs) are created in the lab by reprogramming adult cells, such as skin or blood cells. This process transforms these cells into a state similar to embryonic stem cells, which can develop into diverse cell types within the body. iPSCs can be precisely guided to differentiate into specialized tissues like cardiomyocytes and neurons. They have the same genetic background as individuals affected by a particular disease. This allows us to precisely identify potential treatments tailored to specific disease variants.

For each disease, Perlara’s scientists consider which model would best mirror the effect of the genetic variant, so that the hits we find would be most relevant for the diseases.

Our scientific team will assess the different variants and will recommend the best model for the group.

The use of your established cell line in Perlara's experiments depends on the specific model for the drug screen. If your cell line aligns with the requirements for the drug repurposing screen, we can utilize it. However, if a different cell type is needed, we'll discuss the best way forward—whether it's differentiating your existing cell line into a specific cell type or, if needed, generating a new cell line.

If you don't have a cell line established, Perlara will work with you to establish an appropriate cell line for the given project. We will guide you through the process, provide recommendations on the best practices for storing the cells long-term, and ensure they are preserved effectively and accessible for future studies.

The simplest model is yeast. Maintaining a high degree of similarity between the yeast genome and the human genome, allows us to rapidly evaluate the effect of many drugs. However, there are cases in which a yeast model is not a suitable model for a specific disorder. In these cases, we would opt for a different model, which mirrors the disease better. Drosophila melanogaster, commonly known as the fruit fly, is an exceptional model for studying human diseases. Beyond genetic similarity, the fly possesses sophisticated and complex systems, faithfully mimicking the functions of the mammalian heart, kidneys, gut, lungs, and nervous system. This versatility makes the fruit fly a valuable tool in disease research. Induced Pluripotent Stem Cells (iPSCs) can be precisely guided to differentiate into specialized tissues such as cardiomyocytes and neurons. They have the same genetic background as individuals affected by a particular disease. This allows us to precisely identify potential treatments tailored to specific disease variants.

Perlara offers a range of services to meet the needs of families and patient organizations from receipt of a genetic diagnosis to FDA approval of (a) new therapeutic(s) for their disease. Cure Guide services pair families with one or more Cure Guides who provide scientific and strategic consulting, data analysis, and project management services to help devise the best strategy to develop new treatments for rare genetic diseases and to implement this approach as quickly and economically as possible by partnering with outside organizations or via Perlara research services. In some cases, research services are also available at Perlara’s laboratory facility in Alameda. We currently offer yeast model development, drug screening, and fibroblast tissue culture services. Perlara also has an extensive network of preferred academic and contract partners that can implement additional research services including (but not limited to): model development and drug screening in worms, flies, or patient-derived cells; transcriptomic, proteomic, glycoproteomic, and metabolomic analysis; and mitochondrial activity analysis.

Perlara supports the clinical development of new therapeutic candidates by advising on and assisting with: the patenting process and working with IP attorneys; forming clinical sponsor companies in conjunction with patients or patient groups and securing trial funding; identifying and coordinating with physician-scientists and clinical trialists; and devising a regulatory strategy.

No. Perlara is a company of scientists, and we deliver scientific data and insights to our clients. However, Perlara routinely coordinates with patients’ existing clinical teams and brings in additional healthcare professionals, who can make clinical decisions including prescribing medications. Perlara Cure Guides can present to and discuss with clinicians on behalf of patient families and organizations, but final decisions about clinical care (even when testing over-the-counter medications or supplements) should always be made in conjunction with the patient’s primary physician and clinical care team.

Yes, Perlara has developed an extensive network of specialists across many key areas of rare disease. Your Cure Guide can help connect you to specialists in our network with expertise in your disease area or help establish new relationships if necessary.

Yes, Perlara can negotiate contracts with external parties and manage the progress of external research services on our client’s behalf. Contracts can be between the client and service provider directly, or Perlara can serve as a signatory.

Perlara has a network of preferred service providers that have produced high-quality results at good value for our clients in the past. However, clients always have the final say about which service provider they wish to use.

Perlara’s finance department invoices clients for all project fees on the schedule outlined in the relevant Statement of Work, as well as any pass-along costs such as subcontracts and consumables. Invoices can be paid either via check, wire, or ACH transfer. Contracts made directly between the client and external partners are subject to the relevant partner’s payment terms, even if the contract was negotiated by Perlara on behalf of the client.

We understand that occasionally a client may need to delay or cancel a project due to unforeseen circumstances, and this can be done at any time. Perlara will make every reasonable effort to accommodate requested schedule changes. However, as significant costs are incurred related to project initiation, cancellation/postponement fees will apply. Upon receipt of a signed Statement of Work, Perlara may begin culturing cells or biological material and/or order reagents and/or allocate other resources for the specified project or services. If a client requests postponement of a project start, Perlara will make every effort to accommodate the requested change; however, due to resource constraints and the realities of biological research, Perlara may not be able to reschedule the project precisely as requested by the client. As such, we recommend that clients initiate projects only when they are prepared to fund completion of all deliverables in the Statement of Work. In the event of postponement or cancellation of the project by a client, the client is responsible for all costs incurred to date for work performed and resources secured. Additional compensation may be required for items procured specifically for the project (e.g., biological material, dedicated equipment, perishable or non-reusable supplies) and any non-recoverable expenses incurred by Perlara (e.g., equipment lease payments, subcontractor charges or consultant fees to which Perlara is irrevocably committed). In the event a client terminates or postpones an ongoing project, the Client will be responsible for all fees incurred through the termination date, committed costs and lost opportunity charges.

First and foremost, families provide funding to fuel research. In our experience, when families are also able to go deep into the science, the probability of project success goes up.

Cure Guides are part-time consultants who work with pioneer families. They usually have a PhD or MD (or both) and experience in translating discoveries from the lab to the clinic. Cure Guides provide project management, collaboration management, data analysis, and related scientific consulting services. Cure Guides are not meant to replace experts in your gene/disease. Rather, they complement the expertise of researchers studying a specific disease gene and provide a holistic view of the drug development process.

Yes, a fully enrolled pivotal Phase 3 trial will be completed later this year. We are currently working with several pioneer families on n-of-few observational studies. For example, a n-of-3 study of ibuprofen for MAN1B1-CDG.