Crescent Diagnostics won the award for developing BQT™, a ground breaking diagnostic test to provide an early assessment of the risk of future hip fracture in post-menopausal women using a small toenail clipping. Researchers at University of Limerick, led by Dr Mark Towler, co-founder of Crescent Diagnostics, discovered a relationship between human nail structure, osteoporosis and fracture risk, and were able to demonstrate that the nail is a very effective surrogate for the analysis of bone quality.

Commenting on the award, CEO, Crescent Diagnostics CEO Ernest Poku said: “It is a privilege to receive this award on behalf of my colleagues at Crescent Diagnostics. With a strong international team and a very well-executed study behind us, we have taken a major step forward in the clinical validation required to position BQT™ as an innovative and accurate predictive diagnostic test. Raising market awareness is our next step and this esteemed award is a major boost for our product at this critical juncture.”

Commending Crescent Diagnostics on winning the award, IMDA director Sharon Higgins said: “Despite the current economic climate, we are very much witnessing the fruits of Ireland’s strong and dynamic national innovation strategy. Crescent Diagnostics is making a major contribution towards the establishment of Ireland as an international innovation hub, and we are delighted to honour this pioneering medical devices company. Companies such as Crescent Diagnostics play a crucial role in ensuring that Ireland retains its position as a world leader in the medical technology sector.”

Dublin, Ireland: 22nd June 2011… Crescent Diagnostics Ltd, (“Crescent”) a developer of novel tests for predicting osteoporotic fracture risk, today announced that it has raised Euro 1.5 million ($2.2 million) in Series A funding to support the development of BQT®, a predictive test for the disease.

Crescent’s novel test will enable physicians to diagnose the risk of osteoporosis-related fracture both quickly and easily, using a small nail clipping. The BQT® analyser uses Raman spectroscopy to examine the chemical bonds in the toenail. Crescent’s research has shown that the structure and quantity of the chemical bonds in the human toenail is indicative of future hip fracture risk and is independent of bone mineral density (BMD), the standard test today. When BQT® test development is complete, a physician will be able to send a nail clipping to a laboratory for analysis, with results made available to the patient within a matter of days.

More than 60 million women over 50 are at risk of developing osteoporosis in the US alone and under-diagnosis is a major problem with less than a quarter of at-risk women tested. The current gold standard screening method, Dual X-ray Absorptiometry (DXA), is costly, time consuming for patients and only assesses BMD, which is just one of many risk factors contributing to bone fractures. Many patients with acceptable DXA values still suffer fractures and more accurate tests for fracture risk are therefore required.

The funding round was a syndicated deal between AIB Seed Capital Fund co-managed by Enterprise Equity Venture Capital, Bank of Ireland Seed Fund managed by Kernel Capital, and existing venture investor Seroba BioVentures. The funds will be used to run additional clinical trials and to advance BQT® to regulatory approval in both the US and EU.

Ernie Poku, CEO of Crescent, commented: “There is a massive unmet need for more convenient, accurate and affordable fracture testing. The BQT® test is a novel solution with the potential to significantly enhance osteoporosis diagnosis by evaluating completely different risk factors to DXA. This funding will allow us to complete additional clinical trials and bring BQT® to market.”

For further information please contact:

Europe:
Tony Stephenson
Chempetitive Group
Tel: +44 (0)20 3159 4145 / +44 (0)7899 796655
Email: tstephenson@chempetitive.com

USA:
Kena Hudson
Chempetitive Group
Tel: + 1 501 908 0966
Email: khudson@chempetitive.com

Authors: P. Moran, M. R. Towler, S. Chowdhury, J. Saunders, M. J. German, N. S. Lawson, H. M. Pollock, I. Pillay and D. Lyons

Abstract: Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.

Authors: I. Pillay, D. Lyons, M.J. German, N.S. Lawson, H.M. Pollock, J. Saunders, S. Chowdhury, P. Moran and M.R. Towler.

Background: Anecdotally, patients volunteer reports of increasing hardness of their fingernails within months of starting diverse treatments for osteoporosis. The properties of both nail and bone may be linked in a comparable, measurable way.

Methods: We examined the fingernails of two groups of patients, with (n = 9) and without (n = 13) osteoporosis at either the hip or lumbosacral spine. We performed nanoindentation to assess the degree of nail brittleness and Raman spectroscopy to assess the disulfide bond content of nail.

Results: The mean moduli of fingernails of patients with low bone mineral density (BMD) are lower than those of patients with normal BMD. The mean difference in mean modulus between the groups was found to be 0.996 (p = 0.15 between groups). The spectroscopy data also showed differences between the two sets of nails. The disulfide bond content of the nails sourced from osteoporotic patients was lower than that from healthy patients (p = 0.06 between groups).

Conclusions: Bone collagen and nail keratin are two distinct structural proteins, and both require protein sulfation and disulfide bond formation, via cysteine, for structural integrity. A disorder of either process may lead to disordered collagen and keratin synthesis. This is reflected in the structural abnormalities seen in clinical syndromes in which there is either protein deficiency, disorders of sulfur metabolism, or cystathione beta-synthase deficiency. The relationship between nail and bone may exist in a measurable way. This pilot study should lead to further work to explore this relationship. Could nail prove to be a valuable adjunct to diagnosis or provide a means of more rapid follow-up after commencement of therapy?

Authors: M. R. Towler, A. Wren, N. Rushe, J. Saunders, N. M. Cummins and P. M. Jakeman

Abstract: Dual X-ray absorptiometry (DEXA) is the current gold standard for the diagnosis of osteoporosis. However, patients can suffer osteoporotic fractures despite normal bone mineral density, partly because of unmeasured influences of both the protein and mineral phases of bone that are affected in osteoporosis. There is currently no clinically applicable method of evaluating the health of the protein phase. The proteins in human nail (keratin) and bone (collagen) require sulphation and disulphide bond (S–S) formation for structural integrity and disorders of either sulphur metabolism or cystathione beta-synthase can lead to structural abnormalities in these tissues. Raman protein spectra provide a method of non-invasive measurement of the degree of sulphation of structurally related proteins that may be indicative of bone health. Raman spectroscopy was used to evaluate the disulphide (S–S) content of fingernails. The nail samples came from from 169 women (84 pre- and 85 post-menopausal), of which 39 had a history of osteoporotic fracture. BMD was measured by DXA at the spine. Analyses included parametric and non-parametric tests, dependent on the distribution of the test variable. Mean disulphide content of the nail reduced with age and was slightly higher in pre-, compared to post-menopausal women (P = 0.187). Significantly lower disulphide content was observed in nails obtained from subjects with a history of fracture (P = 0.025). When either disulphide content or BMD was used as a predictor, the odds ratio of these two measures were found to be comparable predictors for fracture status. This suggests that measurements of change in the protein phase of structural proteins such as keratin in the human nail may be correlated with clinically relevant changes in bone proteins that are important in fracture risk

Authors: M. R. Towler, A. Wren, N. Rushe, J. Saunders, N. M. Cummins and P. M. Jakeman

Abstract:

BACKGROUND: The relationship between nail and bone may be measurable, thus making the fingernail a potentially valuable tool for assessing bone health for women receiving treatment for breast cancer. In the BIG 1-98 Fingernail Pilot Substudy, Bone Quality Test (BQT) scores of fingernails were measured at two assessment timepoints.

METHODS: Thirteen eligible patients were enrolled into the substudy during their treatment with tamoxifen (four patients) or letrozole (nine patients). Two fingernails were tested and BQT scores averaged for two assessments six months apart.

RESULTS: BQT scores collected six months later (second assessment) significantly decreased compared with those at first collection (p=0.007) regardless of treatment and prior fracture.

CONCLUSION: The reduction of BQT scores observed in the patients of our small exploratory study during exposure to bone-altering breast cancer treatments is an incentive for larger studies using this technique.