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Background
Benign Prostatic Hyperplasia (BHP) is a common condition affecting older men in which the prostate gland becomes enlarged, which could cause issues associated with urination. Androgenetic Alopecia (AGA) is the most common form of hair loss. Both diseases are mediated by androgens.
The main pathogenic androgen in those conditions (BHP and AGA) is dihydrotestosterone (DHT). DHT is a product of the conversion of testosterone by the enzyme 5-ɑ reductase (5AR).
There are two key isoforms of the 5-a reductase (5AR) enzyme, Type I and Type II. These are encoded by different genes. Understanding the variations in tissue distribution and functionality between these isoforms (Type I and Type II) is crucial for the development of targeted interventions for DHT regulation.
Our goal is to reduce DHT levels in targeted biological systems. This reduction can be achieved through various mechanisms, such as enzyme inhibition, a decrease in enzyme activity, or modulation of gene expression. Novel inhibitors have the potential to contribute to the development of therapies for conditions like BPH and AGA by targeting the overproduction of DHT.
We are seeking tools and screening capabilities (ideally high throughput in nature) to screen novel substances for their potential to inhibit 5-alpha reductase.
What we're looking for
We are looking for high throughput screening systems or models to identify 5-alpha reductase inhibitors (type I & II) through enzyme inhibition, activity reduction, and/or gene expression modulation.
Our must-have requirements are:
- Model(s) capable of screening enzymatic activity of 5 alpha reductase (type I OR II)
- Model must be capable of screening chemical suitable for use in foods, dietary supplements, or pharmaceuticals
Our nice-to-have's are:
- A pre-existing model validated with known reference compounds
- Demonstrated reproducibility (Test can be done in another lab and get the same results when following a protocol.)
- High throughput in nature (ability to screen 20> materials at a time) or inexpensive and quick compared to conventional in-vitro assay technology
What's out of scope:
- Animal or animal derived models or systems; Models or systems that cannot be adapted to use non-animal components
Acceptable technology readiness levels (TRL):
Levels 3-9
What we can offer you
Eligible partnership models:
Sponsored research
Co-development
Licensing
Material transfer
Benefits:
Sponsored Research
Funding is proposal dependent, but an accepted proposal could expect support in the range of 25,000 - 100,000 USD (milestone dependent) with the potential for follow on funding.Expertise
Partners will interact with a project lead to mutually develop a project plan and engage in regular meetings to ensure success. Partners will have access to internal team/experts as appropriate.Q&A with the company
The Q&A is now closed.
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Q.
We study the side effects of 5alpha reductase inhibitors in animal models; are you interested also in this?
3
Q.
Are in-silico methods acceptable?
BS
November 7, 2023
1
Q.
Hi Rob: We do inhibitor development, in high-throughput screening.
Do you: (i) prefer one type of readout; (ii) have trusted enzymes as in-kind; (iii) prefer small or 'large' inhibitors?
LU
December 6, 2023
1
A.
Thank you for the question. We would prefer a readout for isoenzyme I and/or II, however, we would be interested to learn what other readouts might be possible with your assay. If we understand your second question, we do not have an enzyme to provide. We would expect the solution provider to source their own enzyme consistent with what is known in the existing literature / commercial suppliers. In terms of inhibitors, we would expect compounds / substances to largely be small molecules consistent with what is used in nutritional supplements / topical formulations (vs. large molecules, biologics, etc).
Is this response helpful?
0
0
A.
To summarize, in one system you want to discern the inhibition effects of molecules for I and II in the same assay. Is it a deal breaker if I and II are separated into different tests? As for readout, I was trying to ascertain the type of system you prefer for the assay (like fluorescence, ITC of molecules in solution or qcmd/SPR with molecules bound to surfaces). I think with this information we can put in a competitive proposal.
LU
December 7, 2023
1
A.
I appreciate the clarification. It is not a deal breaker if the different types require separate tests.
As far as readouts are concerned each of the different methodologies you've cited have pros and cons and ultimately we'd balance multiple aspects when considering a proposal. For example, an existing assay that could more quickly provide relevant insight may be advantageous over a bespoke assay. Alternatively, a bespoke assay may allow for a greater number of compounds to be tested more quickly and efficiently with more direct insight into the research question. Ultimately, each proposal will be considered on their own merits as well as relative to the other proposals received.
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0
Q.
We encapsulated finasteride in a topical patented slow-release nanoparticle. 2 Clinical studies: up to 4x hair regrowth vs oral due to superior skin & transfolicular penetration, release of up to 190 hrs. Co-development?
1
Q.
Will there be an interest for a high throughput electrophoresis method which is simple, economical, and fully automated. Do we have to propose our own novel inhibitors or just provide a methodology for screening?
SS
December 15, 2023
1
A.
Hi Shahab,
Thanks for reaching out. I'm not 100% certain how you intend to use electrophoresis to screen for 5AR activity, however, if you're are confident it can and that is also has the advantages of being straight forward and cost effective it would definitely be of interest and worth a submission. There is no requirement for proposing your own inhibitors -- proposing a methodology for screening would be sufficient.
Thanks,
Rob
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0
0
Q.
We can use the UV-Vis technique to detect 5 alpha reductase inhibitors in natural products.
Can accurately detect it up to 10 micrograms per liter. This technique is not as sensitive as HPLC.
AH
Ahmad Hassan, Research Development, Damascus University
December 23, 2023
1
Q.
I understand that the applicant must have a system to assay the two 5AR enzymatic activities and inhibition. Does the applicant also have to have compounds with the potential of inhibiting these enzymes?
AS
December 22, 2023
1
Q.
Are 3D human cell culture platforms of interest?
JM
December 4, 2023
1
Is this response helpful?
0
0
Q.
The goal of investigating this enzyme is for research purposes, or to apply it to natural compounds, or to discover new medications for prostate enlargement and other matters? Please explain.
AH
Ahmad Hassan, Research Development, Damascus University
December 23, 2023
1
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